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Prognostic correlation of miRNA expression through microarray in spindle cell carcinoma of penis

Abstract

Introduction: The penile cancer, although rare in Western countries, accounts for up to 20% of male cancers in developing countries. The main penile cancer prognostic factors are the pathological stage and tumor grade, although they are useful in daily practice, these factors have performance below desired. The surgical treatment of localized tumor with penectomy and inguinal lymphadenectomy has high rates of recurrence-free survival; but when there is lymph node involvement the results of surgical treatment is inferior. Additionally the response rates of systemic therapies or radiotherapy are also poor. Published data indicate that epigenetic phenomena, such as the expression of microRNAs (miRNA), plays an important role in carcinogenesis of several malignancies. We postulate that a particular miRNA expression profile may be associated with poorer prognosis of penile cancer, and that this knowledge might lead to the discovery of new prognostic markers. Objective: To identify the pattern of miRNA expression in localized penile câncer treated by surgery and associate it with the behavior of the disease. The ultimate goal is the identification of markers of tumor aggressiveness that can serve as prognostic and target therapy biomarkers. Methodology: In the initial phase, we will analyze frozen tissue samples from primary tumor of 12 patients with penile cancer divided into two groups: (a) six low grade and low stage tumors; and (b) six patients with high grade and locally advanced tumors. The samples will be subjected to miRNA expression analysis employing the microarray technique in order to identify the miRNAs most differentially expressed when compared good versus poor prognosis cases. For the validation phase we will prospectively evaluate 20 patients with localized or locally advanced penile squamous cell carcinoma, treated with surgery and with a postoperative follow-up of 3 years (group c). We will collect fresh frozen samples from the primary tumors and inguinal lymphadenectomy product of these 20 cases to validate the miRNAs previously selected in the initial phase, these miRNAS expression levels will be evaluated by Real Time PCR techinique. Then we will correlate the miRNA expression levels with pathological stage, tumor grade, angiolymphatic invasion and tumor recurrence-free survival. The presence of HPV DNA will be evaluated by PCR followed by the sequencing methodology. (AU)

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